Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Aug 2010
Co-administration of ultra-low dose naloxone attenuates morphine tolerance in rats via attenuation of NMDA receptor neurotransmission and suppression of neuroinflammation in the spinal cords.
Although mechanisms underlying ultra-low dose naloxone-induced analgesia have been proposed, possible interactions with glutamatergic transmission and glial cell activation have not been addressed. In the present study, we examined the effect of ultra-low dose naloxone on spinal glutamatergic transmission and glial cell activity in rats chronically infused with morphine. In male Wistar rats, intrathecal morphine infusion (15microg/h) for 5days induced (1) antinociceptive tolerance, (2) downregulation of glutamate transporters (GTs) GLT-1, GLAST, and EAAC1, (3) increasing of NMDA receptor (NMDAR) NR1 subunit expression and phosphorylation, (4) upregulation of protein kinase C gamma (PKCgamma) expression, and (5) glial cell activation. ⋯ These effects may result in preservation of the antinociceptive effect of acute morphine challenge in chronic morphine-infused rats. Ultra-low dose naloxone infusion alone did not produce an antinociceptive effect. These findings demonstrated that attenuation of glutamatergic transmission and neuroinflammation by ultra-low dose naloxone co-infusion preserves the lasting antinociceptive effect of morphine in rats chronically infused with morphine.
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Pharmacol. Biochem. Behav. · Jul 2010
Randomized Controlled Trial Comparative StudyCannabis with high δ9-THC contents affects perception and visual selective attention acutely: an event-related potential study.
Cannabis intake has been reported to affect cognitive functions such as selective attention. This study addressed the effects of exposure to cannabis with up to 69.4mg Delta(9)-tetrahydrocannabinol (THC) on Event-Related Potentials (ERPs) recorded during a visual selective attention task. ⋯ Performance requiring attentional resources, such as vehicle control, may be compromised several hours after smoking cannabis cigarettes containing high doses of THC, as presently available in Europe and Northern America.
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Pharmacol. Biochem. Behav. · Jul 2010
Comparative StudyPotentiation of morphine antiallodynic efficacy by ACPT-III, a group III metabotropic glutamate receptor agonist, in rat spinal nerve ligation-induced neuropathic pain.
Despite the importance of spinal metabotropic glutamate receptors (mGluRs) and opioid receptors in nociceptive processing, the roles of these receptors in the modulation of neuropathic pain at the spinal level have not been thoroughly investigated. The purpose of this study was to investigate the effects of spinal mGluR agents and opioids (morphine) on neuropathic pain. Male Sprague-Dawley rats underwent L5 and L6 spinal nerve ligation to induce neuropathic pain and intrathecal catheterization for drug administration. ⋯ Whereas ACPT-III, a Group III mGluR agonist, enhanced the antiallodynic action of morphine, other mGluR agents did not. Collectively, mGluRs may not directly modulate the processing of spinal nerve ligation-induced neuropathic pain at the spinal level. However, Group III mGluR agonists in the spinal cord may indirectly contribute to the potentiation of morphine antiallodynia, indicating that these agonists might be used as adjuvants for spinal morphine.
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Pharmacol. Biochem. Behav. · Jun 2010
Comparative StudyThe CB1 inverse agonist AM251, but not the CB1 antagonist AM4113, enhances retention of contextual fear conditioning in rats.
The effects of CB1 antagonist/inverse agonists on the acquisition and consolidation of conditioned fear remain uncertain. Recent studies suggest that the CB1 antagonist/inverse agonist AM251 affects acquisition or consolidation of both contextual and discretely cued fear memories. AM251 is frequently referred to as a CB1 antagonist; however in vitro signal transduction assays indicate that this drug also elicits inverse agonist activity at CB1 receptors. ⋯ In contextual fear retention tests, animals previously treated with 4.0 or 8.0 mg/kg AM251 exhibited enhanced freezing. By contrast, no dose of AM4113 had any significant effect on contextual fear memory, which is consistent with the lower signal transduction activity of AM4113 at CB1 receptors compared to AM251. These results suggest that CB1 neutral antagonists may be less likely than CB1 inverse agonists to facilitate the acquisition or consolidation of contextual fear that may contribute to some clinical disorders.
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Pharmacol. Biochem. Behav. · Jun 2010
Comparative StudyGABA(A) receptor antagonism in the ventrocaudal periaqueductal gray increases anxiety in the anxiety-resistant postpartum rat.
Postpartum mammals show suppressed anxiety, which is necessary for their ability to appropriately care for offspring. It is parsimonious to suggest that the neurobiological basis of this reduced anxiety is similar to that of non-parturient animals, involving GABA(A) receptor activity in sites including the midbrain periaqueductal gray (PAG). In Experiment 1, postpartum and diestrous virgin female rats received an intraperitoneal injection of the GABA(A) receptor antagonist (+)-bicuculline (0, 2 and 4 mg/kg) and anxiety-related behavior was assessed with an elevated plus maze. ⋯ Experiment 2 revealed that bicuculline's action was within the central nervous system, because anxiety in neither dams nor virgins was significantly affected by intraperitoneal injection of bicuculline methiodide (0, 2 and 6 mg/kg), which does not readily cross the blood-brain-barrier. In Experiment 3, bicuculline methiodide (2.5 ng/side) was directly infused into the ventrocaudal PAG (cPAGv) and significantly increased dams' anxiety compared to saline-infused controls. These studies expand our knowledge of how GABA(A) receptor modulators affect anxiety behaviors in postpartum rats to the widely-used elevated plus maze, and indicate that the postpartum suppression of anxiety is in part a consequence of elevated GABAergic neurotransmission in the cPAGv.